Sara Lemoinne1, Albert Pares2, Anna Reig3, Karima Ben Belkacem4, Astrid Donald Kemgang Fankem5, Farid Gaouar6, Raoul Poupon7, Chantal Housset8, Christophe Corpechot9, Olivier Chazouillères10. 1. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; INSERM, Sorbonne université, centre de recherche Saint-Antoine (CRSA), faculté de médecine, site Saint-Antoine, 27, rue de Chaligny, 75012 Paris, France. Electronic address: sara_lemoinne@yahoo.fr. 2. IDIBAPS, CIBERehd, Liver Unit, Hospital Clínic, Univesity of Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Electronic address: apares@clinic.cat. 3. IDIBAPS, CIBERehd, Liver Unit, Hospital Clínic, Univesity of Barcelona, Carrer de Villarroel, 170, 08036 Barcelona, Spain. Electronic address: anna.rg86@gmail.com. 4. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; INSERM, Sorbonne université, centre de recherche Saint-Antoine (CRSA), faculté de médecine, site Saint-Antoine, 27, rue de Chaligny, 75012 Paris, France. Electronic address: karima.benbelkacem@aphp.fr. 5. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; INSERM, Sorbonne université, centre de recherche Saint-Antoine (CRSA), faculté de médecine, site Saint-Antoine, 27, rue de Chaligny, 75012 Paris, France. Electronic address: kastriddonald@yahoo.fr. 6. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France. Electronic address: farid.gaouar@aphp.fr. 7. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France. Electronic address: Raoul.poupon@orange.fr. 8. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; INSERM, Sorbonne université, centre de recherche Saint-Antoine (CRSA), faculté de médecine, site Saint-Antoine, 27, rue de Chaligny, 75012 Paris, France. Electronic address: Chantal.housset@inserm.fr. 9. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; INSERM, Sorbonne université, centre de recherche Saint-Antoine (CRSA), faculté de médecine, site Saint-Antoine, 27, rue de Chaligny, 75012 Paris, France. Electronic address: Christophe.corpechot@aphp.fr. 10. Hepatology department, reference center for inflammatory biliary diseases and autoimmune hepatitis, Saint-Antoine Hospital, Assistance publique-Hôpitaux de Paris, 184, rue du Faubourg-Saint-Antoine, 75012 Paris, France; INSERM, Sorbonne université, centre de recherche Saint-Antoine (CRSA), faculté de médecine, site Saint-Antoine, 27, rue de Chaligny, 75012 Paris, France. Electronic address: Olivier.chazouilleres@aphp.fr.
Abstract
BACKGROUND & AIMS: In patients with primary sclerosing cholangitis (PSC), ursodeoxycholic acid (UDCA) treatment improves serum liver tests and surrogate markers of prognosis but has no proven effect on survival. Additional therapies are obviously needed. Fibrates, PPAR agonists with anti-cholestatic properties, have a beneficial effect in primary biliary cholangitis. The aim of this study was to evaluate the safety and efficacy of fibrates in PSC patients. METHODS: Retrospectively, we investigated PSC patients treated with fibrates (fenofibrate 200mg/day or bezafibrate 400mg/day) for at least 6 months in addition to UDCA, after an incomplete biochemical response (alkaline phosphatase [ALP] ≥1.5×upper limit of normal) to UDCA. Changes in biochemical parameters and clinical features were assessed. RESULTS: Twenty patients were included (fourteen from Paris and six from Barcelona): median age 43.8 years, median liver stiffness 11kPa (≥F3). Upon treatment with fibrates (median duration of 1.56 years), liver tests significantly improved, including a reduction of ALP levels by 41% and pruritus significantly decreased. No serious adverse event attributable to fibrates occurred. Discontinuation of fibrates was followed by a clear rebound of ALP. Despite biochemical improvement, liver stiffness significantly increased. CONCLUSIONS: Combining UDCA with fibrates results in a significant biochemical improvement and pruritus decrease in PSC patients with incomplete response to UDCA. These results provide a rationale for larger and prospectively designed studies to establish the efficacy and safety of fibrates in PSC.
BACKGROUND & AIMS: In patients with primary sclerosing cholangitis (PSC), ursodeoxycholic acid (UDCA) treatment improves serum liver tests and surrogate markers of prognosis but has no proven effect on survival. Additional therapies are obviously needed. Fibrates, PPAR agonists with anti-cholestatic properties, have a beneficial effect in primary biliary cholangitis. The aim of this study was to evaluate the safety and efficacy of fibrates in PSC patients. METHODS: Retrospectively, we investigated PSC patients treated with fibrates (fenofibrate 200mg/day or bezafibrate 400mg/day) for at least 6 months in addition to UDCA, after an incomplete biochemical response (alkaline phosphatase [ALP] ≥1.5×upper limit of normal) to UDCA. Changes in biochemical parameters and clinical features were assessed. RESULTS: Twenty patients were included (fourteen from Paris and six from Barcelona): median age 43.8 years, median liver stiffness 11kPa (≥F3). Upon treatment with fibrates (median duration of 1.56 years), liver tests significantly improved, including a reduction of ALP levels by 41% and pruritus significantly decreased. No serious adverse event attributable to fibrates occurred. Discontinuation of fibrates was followed by a clear rebound of ALP. Despite biochemical improvement, liver stiffness significantly increased. CONCLUSIONS: Combining UDCA with fibrates results in a significant biochemical improvement and pruritus decrease in PSC patients with incomplete response to UDCA. These results provide a rationale for larger and prospectively designed studies to establish the efficacy and safety of fibrates in PSC.
Authors: Gina M Gallucci; Jocelyn Trottier; Christopher Hemme; David N Assis; James L Boyer; Olivier Barbier; Nisanne S Ghonem Journal: Hepatol Commun Date: 2021-08-27
Authors: Nisanne S Ghonem; Adam M Auclair; Christopher L Hemme; Gina M Gallucci; Randolph de la Rosa Rodriguez; James L Boyer; David N Assis Journal: Clin Pharmacol Ther Date: 2020-07-17 Impact factor: 6.875